1. Field of the Invention
The invention relates to novel methods and instruments for evaluating the strength of human and animal bones.
2. Related Art
Recent measurements of materials properties of bone have demonstrated that there is substantial deterioration of these properties with aging. For example, Nalla, Kruzic, Kinney, & Ritchie, have shown that the stress necessary to initiate cracks in the bone, the initiation toughness, decreases by 40% over 6 decades from 40 to 100 years in human bone even without diagnosed bone disease. Even more dramatically, the crack-growth toughness is effectively eliminated over the same age range [1] This recent research extends and supports earlier research that showed a significant deterioration in another materials property, fracture toughness, with age [2-11]. These measurements suggest that deteriorating materials properties of bone due to aging or disease may play a role in bone fracture risk in addition to the well known factors of decrease in bone mineral density and deterioration of micro architecture.
Fracture risk is now commonly assessed by measuring bone mineral density (BMD) through various techniques including dual energy x-ray absorptiometry, quantitative ultrasound and others. These techniques all measure properties of bone without inducing fracture at any length scale. They are generally believed to be incomplete measures of fracture resistance. This is especially true for young, healthy people, such as Army recruits, for whom these conventional measures of bone fracture risk have been found to be ineffective in assessing fracture risk during basic training [12]. Further, it is known that these measurements, though valuable, do not fully characterize fracture risk in elderly patients or in patients with osteoarthritis, osteoporosis or other bone disease.
Osteoporosis is a major public health concern according to the World Health Organization (WHO) [13]. While 50 million women worldwide suffer from the disease, osteoporosis and osteopenia (low bone mass) are frequently associated with increased age, but both diseases affect people in every stage of life, having a huge impact on people in the workforce. The economic burden of osteoporosis is expected to reach $131.5 billion by 2050[14]. Healthcare costs in the United States currently exceed $15 billion annually for osteoporosis related treatment [15].
Osteopenia and osteoporosis are frequently asymptomatic and diagnosis is often not ascertained until a fracture has occurred or until a low bone mineral density (BMD) has been determined. The most significant complication of osteoporosis is fracture, often induced by trauma of a very low magnitude [16]. For many, a fracture may mean loss of mobility along with life quality and increased risk of mortality. Numerous interventions have been shown to reduce the risk of fracture in this population; however, despite the overwhelming number of patients falling into the fracture risk categories, facilities for evaluations are inadequate and only those evaluated as the highest risk are adequately tested and treated. The vast majority of those at risk are unevaluated, due to costs considerations [17].
Initially, most patients are subjected to assessment instruments that strive to identify those at risk of low bone mineral density OST (Osteoporosis Self Assessment Tool), SCORE (Simple Calculated Osteoporosis Risk Estimation), SOFSURF (Study of Osteoporotic Fractures) and OSIRIS (Osteoporosis Index of Risk) are representative of these and often are used by practitioners to determine those cases most in need of BMD measurements while simultaneously improving patient awareness of risk factors. Tests are based on body weight, age and several additional factors. While these tests have a high sensitivity (up to 90%) there are many limitations in accuracy specific to each individual [18].
A plethora of diagnostic Instruments are currently in use for assessing fracture risk in patients, focusing on decrease in bone mineral density and deterioration of micro architecture. Dual-energy x-ray absorptiometry (DEXA) has been used to clinically measure these factors. Bone mineral density currently remains the most widely accepted indicator of fracture risk and is also used for true diagnosis of osteoporosis. DEXA is most commonly accepted as the instrument of choice and is used as the main determinant in evaluating risk, but numerous drawbacks and limitations have been observed. Discrepancies between instruments may have a serious effect on the diagnosis and treatment of patients [19]. Additionally, patients with normal BMD may experience fractures while those with low BMD may be at low risk [18]. Criteria are based on World Health Organizations recommendations and T-Scores exhibit discrepancies depending on the assessment sites. While proposals recommended DEXA evaluations of the hip, a higher incidence of greater bone loss in the spine than in the hip 10 years prior to and shortly after menopause has been reported [20]. Improved functions used to evaluate BMD have been recommended to encompass the distinct periodicity of bone development: adolescence, adult stability and reduction with age [21]. BMD results often fail to adequately diagnose children with high fracture risk.
Quantitative Ultrasound (QUS) has been investigated to determine its usefulness as a diagnostic tool for BMD. The equipment is less expensive than DEXA and is radiation free. An osteoporosis and ultrasound study recruited women between the age of 55 and 79. A comparison was done between DEXA and QUS. Results showed good correlation in predicting future incidence of low trauma fractures [22]. While this instrument may be useful for healthy children and postmenopausal women, the high rate of precision errors and large discrepancies in results ascribed to the diametric variations in calcaneus regions bring its usefulness into question [23]. In another study, osteoporotic patients had a lower QUS than controls but there was a large overlap of values [24]. Calcaneus ultrasound may provide a method of assessment for children with osteopenia and with fragility fractures. K. T. Fielding's research indicates results in Z scores similar to those achieved with DEXA but with only a modest correlation [25].
Peripheral quantitative computed tomography (pQCT) has also been studied in hopes of finding a useful tool for establishing bone fracture risk and was found to be less sensitive than DEXA and determined as a poor assessment tool for discriminating those with fractures [26]. In another investigation, pQCT does seem to be a reliable tool for calculating bone Calcium concentrations [27].
Development of morphometric X-ray Absorptiometry was investigated for determining vertebral deformities. High variability in analysis was determined with inter-operator assessment and the precision of analysis declined relative to complexity of the vertebral shape [28].
X-Ray radiogrammetry used routinely in management of patients with distal forearm fractures has been tested as a means of determining BMD and found to be useful in these instances as an alternative to DEXA without requiring further irradiation [29] but is not considered as an alternative to DEXA for alternate diagnoses.
With the exception of pOCT and DEXA, which quantify calcium content as well as BMD, each of these instruments strives to quantify only bone mineral density. While this is a valuable tool in bone strength indication, it overlooks many other aspects of bone that may well be equally important in determining fracture resistance. Tissue quality along with the size, shape and architecture of bone all influence strength and fragility factors [30,31].
Blood tests are sometimes prescribed to evaluate other conditions that influence bone strength. These cover a wide range of activities from alkaline phosphatase and thyroid stimulating hormone to vitamin D and calcium levels. Many of these tests may be beneficial in diagnostics and in determining treatment protocols [32].
In recent years, the value of indentation techniques in the investigation of the mechanical properties of biological materials including bone, dentin and cartilage has been realized [5, 16, 33-42]. Intrinsic toughness characterizes the resistance of mineralized tissues to cracking and fracture. Indentation protocols offer a means to quantify both the toughness and hardness of the biomaterials [1]. Examinations of the dentin-enamel junction of teeth further confirm the value of indentation protocols for understanding crack propagation and fracture mechanics. Using a Vickers indentation instrument, Imbeni et al. were able to characterize how cracks propagate and where crack-arrest barriers appear. Toughness and hardness factors for the enamel, dentin and the interface between the two were quantified [43]. Vickers indentation testing would, however, be difficult on a living patient because of the need to image, at high resolution, the indentations and the cracks that propagate from the corners of the indentations.
Indentation instruments also currently exist that are designed for use under surgical conditions. One such instrument has been designed to measure the stiffness of cartilage through arthroscopic surgical control [44, 45]. Biomechanical property changes in articular cartilage are early indicators of degeneration in the tissues. A reduction in compressive stiffness of articular cartilage is related primarily to the reduction of proteoglycan content and early detection offers possibilities for treatment to arrest the conditions leading to the degenerative process [44]. A similarly designed instrument was used for measurement of structural properties of the cartilage present near the metacarpal bones in Equine species and the results correlated positively with glycosaminoglycan levels in the tissues [46]. An arthroscopic cartilage indenter has been recently used to detect cartilage softening as the early mechanical sign of degradation not yet visible to the eye [47].
Another instrument, the Osteopenetrometer, was designed for in vivo testing of trabecular bone during surgical procedures. This instrument was developed to characterize the mechanical properties of trabecular bone to obtain information relevant to reducing the problem of implant loosening following total knee arthroplasty [48]. The Osteopenetrometer involved penetrations of lengths of order 8 millimeters and widths of order millimeters in diameter at implant sites during surgery. The goal was to have large enough penetrations to average over many trabeculae inside the trabecular bone.
While each of these advances in technology and diagnostic instrumentation produce significant and valuable data toward accurate diagnosis of bone fragility and osteoporosis, they each require skilled technicians. The limitations of available equipment to assess the growing, aging population, and the high expense incurred when diagnostics are available make these tools prohibitive to many patients that are at high risk for fracture. There exists, to our knowledge, no instrument that can clinically measure the material properties of bone relevant to fracture risk in living subjects without surgical exposure of the bone, including removal of the periosteum. The need for an inexpensive diagnostic tool to assess fracture risk within the clinical environment seems clear. While many researchers are still trying to set standards for evaluations of BMD, many also acknowledge its limitations; such as, the uncertainty of applicability to those who have not yet reached their peak bone mass, and the need for adjustments to results based on anatomical location, bone geometry and ethnic background. There is a strong need for a diagnostic instrument with low cost and low labor requirements that can directly determine indications of fracture risk through microcrack inducement, to enable multitudes of “at risk” patients to receive preventative therapy before suffering a fracture.